Phase 1 Completed N=16 Basic Science

A Study of Effect of Multiple Doses of LOXO-305 on the Pharmacokinetics of Single Oral Doses of CYP1A2, CYP2C9, CYP2C19 Substrates in Healthy Participants

Healthy

Source: ClinicalTrials.gov NCT06215430 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Mar 2025

Primary outcomePrimary: Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine — 39100; 37400 hour*nanogram per milliliter (h*ng/mL)

Summary

The main purpose of this study is to evaluate the effect of LOXO-305 on single oral dose of caffeine cytochrome P450 1A2 (CYP1A2) substrate, S-warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate) when administered as multiple doses by collecting the blood samples and conducting the blood tests to measure how much LOXO-305 is in the bloodstream and how the body handles and eliminates LOXO-305 in adult healthy participants. The study will also evaluate the safety and tolerability of LOXO-305. The study will be conducted in two periods. Participants will stay in this study for up to 67 days, including screening.

Outcome Measures

Outcome	Result	p-value
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine	39100; 37400	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Paraxanthine	20600; 18600	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole	2000; 3120	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Warfarin	7320; 7880	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Pirtobrutinib	119000	—
PRIMARY Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Caffeine	39100; 37400	—
PRIMARY Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine	20600; 19400	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole	1990; 3110	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Warfarin	17300; 19200	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Pirtobrutinib	119000	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Caffeine	42600; 40000	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine	23100; 20300	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole	2000; 3120	—
PRIMARY Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin	20100; 22400	—
PRIMARY Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine	5.20; 4.17	—
PRIMARY Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine	12.0; 7.45	—
PRIMARY Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole	0.421; 0.302	—
PRIMARY Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin	13.1; 13.4	—
PRIMARY Apparent Systemic Clearance (CL/F): Caffeine	4.70; 5.00	—
PRIMARY Apparent Systemic Clearance (CL/F): Omeprazole	20.0; 12.8	—
PRIMARY Apparent Systemic Clearance (CL/F): Warfarin	0.497; 0.447	—
PRIMARY Apparent Systemic Clearance (CL/F): Pirtobrutinib	1.68	—
PRIMARY Maximum Observed Plasma Concentration (Cmax): Caffeine	5060; 4990	—
PRIMARY Maximum Observed Plasma Concentration (Cmax): Paraxanthine	1200; 1150	—
PRIMARY Maximum Observed Plasma Concentration (Cmax): Omeprazole	901; 1350	—
PRIMARY Maximum Observed Plasma Concentration (Cmax): Warfarin	585; 595	—
PRIMARY Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib	9430	—
PRIMARY Time to Maximum Observed Plasma Concentration (Tmax): Caffeine	0.500; 0.750	—
PRIMARY Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine	10.0; 8.01	—
PRIMARY Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole	2.00; 2.50	—
PRIMARY Time to Maximum Observed Plasma Concentration (Tmax): Warfarin	1.50; 1.50	—
PRIMARY Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib	2.50	—
PRIMARY Apparent Terminal Elimination Rate Constant (λZ): Caffeine	0.116; 0.127	—
PRIMARY Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine	0.0966; 0.120	—
PRIMARY Apparent Terminal Elimination Rate Constant (λZ): Omeprazole	0.611; 0.578	—
PRIMARY Apparent Terminal Elimination Rate Constant (λZ): Warfarin	0.0160; 0.0165	—
PRIMARY Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine	40.4; 39.4	—
PRIMARY Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole	32.8; 22.2	—
PRIMARY Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin	31.0; 27.1	—
PRIMARY Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine	0.528; 0.518	—
PRIMARY Mean Residence Time (MRT): Caffeine	8.58; 8.03	—
PRIMARY Mean Residence Time (MRT): Paraxanthine	12.8; 10.9	—
PRIMARY Mean Residence Time (MRT): Omeprazole	3.22; 3.58	—
PRIMARY Mean Residence Time (MRT): Warfarin	56.8; 57.9	—
PRIMARY Apparent Terminal Elimination Half-Life (t1/2): Caffeine	5.96; 5.47	—
PRIMARY Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine	7.17; 5.79	—
PRIMARY Apparent Terminal Elimination Half-Life (t1/2): Omeprazole	1.13; 1.20	—
PRIMARY Apparent Terminal Elimination Half-Life (t1/2): Warfarin	43.2; 42.0	—

Eligibility Criteria

Inclusion Criteria

Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m^2), inclusive.
Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator.
Female participants of non-childbearing potential and male participants who follow standard contraceptive methods.
Must have comply with all study procedures, including the 23-night stay at the Clinical Research Unit (CRU) and follow-up phone call.

Exclusion Criteria

History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor.
Known ongoing alcohol and/or drug abuse within 2 years prior to Screening.
History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT06215430). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.